Influenza A viruses (IAV) are significant human pathogens causing yearly epidemics and occasional pandemics. Past pandemics have resulted in significant morbidity and mortality. The 1918 influenza pandemic was thought to have resulted in the death of at least 675,000 people in the U.S. and 40 million people worldwide. Pandemics in 1957 and 1968, while less severe, were also of major public health importance. A novel influenza A virus of swine origin became pandemic in 2009, causing the first pandemic in 41 years. In addition, annual epidemic influenza cases are also very significant resulting in approximately 36,000 deaths in the US annually. It is important to develop clinical natural history studies to compare natural infections with the new H1N1 pandemic virus with those from seasonal influenza viruses. The major goal of this project is to evaluate the natural history of pandemic influenza virus infection in comparison to infection with seasonal influenza viruses in both immunocompromised and non-immunocompromised patients. We plan to recruit up to 1000 patients with pandemic or seasonal influenza virus infection. Recruitment will occur in both inpatient and outpatient settings at multiple sites including the NIH Clinical Center, Suburban Hospital and the Washington Hospital Center. Careful clinical evaluation, analysis of viruses collected from patients, and studies of the immune response of the patients will be performed.